Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

Abstract

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.

Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

“…When exposed to external stress, such as ROS, the Nrf2 inducer reacts with Keap1 cysteine to release Nrf2 protein, which subsequently translocates to the cell nucleus, where it activates Nrf2 and downstream antioxidant enzymes [ 17 ]. As a transcription factor, nuclear Nrf2 induces many target gene transcription, such as HO-1, NADPH, GST, and thioredoxin [ 36 ]. Nrf2 could exert both antioxidant and anti-inflammatory roles [ 37 , 38 , 39 ].…”

“…The inflammation-related pathway, NF-κB, and nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome could also be modulated by Nrf2 [ 40 ]. The lipid peroxidation, oxidative stress, and inflammation could be inhibited by hydroxytyrosol via upregulating Nrf2 in the pancreatitis-associated gut injury [ 36 ]. HO-1 is an inducible rate-limiting enzyme for heme catabolism in the microsomal enzyme system.…”

The Methyl Ester of 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid Reduces Endometrial Lesions Development by Modulating the NFkB and Nrf2 Pathways

“…The levels of reduced GSH were determined in endometriosis lesions and hippocampi to evaluate the endogenous antioxidant defenses. GSH levels were determined using a microplate reader at 412 nm and expressed as ng/mg wet tissue [ 52 , 53 ].…”

Hidrox® and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain

“…The levels of reduced glutathione (GSH) were determined in endometriosis lesions and hippocampi to evaluate the endogenous antioxidant defenses. GSH levels were determined using a microplate reader at 412 nm and expressed as ng/mg wet tissue [ 36 , 37 ].…”